Modulation of interleukin-1β mediated inflammatory response in human astrocytes by flavonoids: Implications in neuroprotection
Abstract
The proinflammatory cytokine interleukin-1beta (IL-1beta) contributes to inflammation and neuronal death in CNS injuries and neurodegenerative pathologies, and astrocytes have been implicated as the primary mediators of IL-1beta induced neuronal death. As astrocytes play an important role in supporting the survival and functions of neurons, we investigated the effect of plant flavonoids quercetin and luteolin, with known anti-inflammatory properties in modulating the response of human astrocytes to IL-1beta for therapeutic intervention. Flavonoids significantly decreased the release of reactive oxygen species (ROS) from astrocytes stimulated with IL-1beta. This decrease was accompanied by an increase in expression of superoxide dismutase (SOD-1) and thioredoxin (TRX1)-mediators associated with protection against oxidative stress. Flavonoids not only modulated the expression of astrocytes specific molecules such as glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), and ceruloplasmin (CP) both in the presence and absence of IL-1beta but also decreased the elevated levels of proinflammatory cytokine interleukin-6 (IL-6) and chemokines interleukin-8 (IL-8), interferon-inducible protein (IP-10), monocyte-chemoattractant protein-1 (MCP-1), and RANTES from IL-1beta activated astrocytes. Significant decrease in neuronal apoptosis was observed in neurons cultured in conditioned medium obtained from astrocytes treated with a combination of IL-1beta and flavonoids as compared to that treated with IL-1beta alone. Our result suggests that by (i) enhancing the potential of activated astrocytes to detoxify free radical, (ii) reducing the expression of proinflammatory cytokines and chemokines, and (iii) modulating expression of mediators associated with enhanced physiological activity of astrocyte in response to injury, flavonoids confer (iv) protection against IL-1beta induced astrocyte mediated neuronal damage.
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Quercetin attenuates IL-1β-mediated inflammation in astrocytes and neuronal cultures by inhibiting release of IL-6 and IL-8.
“quercetin has been demonstrated to attenuate the inflammation mediated by IL-1β in astrocytes and neuronal cultures by inhibiting the release of IL-6 and IL-8 (Sharma et al., 2007)”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Sharma et al., 2007
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- Authors
- Sharma, V., Mishra, M., Ghosh, S., Tewari, R., Basu, A., Seth, P., & Sen, E.
- Affiliations
- National Brain Research Centre (IN)
- Corresponding author
- Sen, Ellora
- Venue
- Brain Research Bulletin
- Publisher
- Elsevier BV
- Published
- 2007-06
- Volume
- 73
- Issue
- 1-3
- Pages
- 55-63
- ISSN
- 0361-9230 (ISSN-L)
- OpenAlex
- W2109107050
- Cited by
- 202
- References
- 47
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 8 · 2023: 9 · 2022: 11 · 2021: 18 · 2020: 8 · 2019: 5 · 2018: 11 · 2017: 10 · 2016: 12 · 2015: 9 · 2014: 15 · 2013: 9 · 2012: 11
- FWCI
- 9.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research Bulletin (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Brain Research Centre
- Topics
- Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Keywords
- IL-1β, astrocytes, flavonoids, quercetin, luteolin, neuroprotection, reactive oxygen species, oxidative stress, superoxide dismutase, thioredoxin, inflammatory cytokines, chemokines, glial fibrillary acidic protein, glutamine synthetase, ceruloplasmin, neuronal apoptosis, neuroinflammation
- MeSH terms
- Astrocytes, Cells, Cultured, Fetus, Flavonoids, Humans, Inflammation, Quercetin, Blotting, Western, Cytokines, Apoptosis, Reactive Oxygen Species, Neuroprotective Agents, Inflammation Mediators, In Situ Nick-End Labeling, Luteolin, Interleukin-1beta
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